In:
Respiration, S. Karger AG, Vol. 74, No. 4 ( 2007), p. 447-453
Abstract:
〈 i 〉 Background: 〈 /i 〉 House dust mites (HDM) have been shown to be important sources of indoor allergens associated with asthma and other allergic conditions. While exogenous proteases from allergens have a direct proinflammatory role in the respiratory tract, the precise mechanisms underlying the release of cytokines from the respiratory epithelium are unclear. 〈 i 〉 Objectives: 〈 /i 〉 The present study examines that extracellular signal-regulated kinase (ERK) activated downstream of the Ca 〈 sup 〉 2+ 〈 /sup 〉 -sensitive tyrosine kinase plays an important role in the efficient activation of the HDM-induced IL-8 signaling pathway. 〈 i 〉 Methods: 〈 /i 〉 We examined the effect of HDM, and the role of the Ca 〈 sup 〉 2+ 〈 /sup 〉 /calmodulin system and mitogen-activated protein kinases, on IL-8 expression in human lung epithelial cells. 〈 i 〉 Results: 〈 /i 〉 In H292 cells, HDM induced IL-8 release in a time- and/or dose-dependent manner. This IL-8 release was abolished by treatment with intracellular Ca 〈 sup 〉 2+ 〈 /sup 〉 chelator (BAPTA-AM), but not by EGTA or nifedipine. Calmodulin inhibitor (calmidazolium) and tyrosine kinase inhibitor (genistein) almost completely blocked IL-8 release by HDM. PD98059, an ERK pathway inhibitor, completely abolished HDM-induced IL-8 release. Moreover, PD98059, BAPTA-AM, calmidazolium and genistein suppressed the HDM-induced ERK phosphorylation. 〈 i 〉 Conclusions: 〈 /i 〉 HDM-induced IL-8 production is predominantly regulated by Ca 〈 sup 〉 2+ 〈 /sup 〉 /calmodulin signaling, and ERK plays an important role in signal transmission for efficient activation of the HDM-induced IL-8 signaling pathway.
Type of Medium:
Online Resource
ISSN:
0025-7931
,
1423-0356
Language:
English
Publisher:
S. Karger AG
Publication Date:
2007
detail.hit.zdb_id:
1464419-8
detail.hit.zdb_id:
206674-9
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